ARE WE ALL SET ? WELL PREPARED FOR NEW

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ARE WE ALL SET ? WELL PREPARED FOR NEWOLD
THREATS!!

• SOMSAK WATTANASRI,MD.
• BOARD OF PEDIATRICS,FETP

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September 11, 2001
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BSE (1987-2000)
NIPAH VIRUS (March 1999)
Influenza A (H5N1) 1997
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• ???????????????????
• 70 ????
• ????????????????? !
• ???????????????
• ????????

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?????????????????????????????????????? ???????????
?????????????????????????????
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????????????????????????
HONG KONG
THAILAND
International airports during SARS crisis, 2003
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INFLUENZA
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Outbreaks g Widespreadg Regionalg Localg Sporadicg Negligibal or no surveillance Outbreaks g Widespreadg Regionalg Localg Sporadicg Negligibal or no surveillance                                                              
Influenza

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Influenza

• Type A, B, or C
• family Orthomyxoviridae

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Type A influenza

• contagious ???????? ????????? acute respiratory
  disease ????????????????? ???????????
• ?? ??? ??? ??????????????????????
• ?????????????? ????? cattle
• sporadic influenza A virus ?????????????????????
  ???????? ?????????????

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Type B and C influenza

• ?????????????
• influenza B ????????????????????????????????????
  ???????????????????????? pandemic ??????
  influenza A ???????????????????????????

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??????? influenza virus

• type (A, B, C)
• ???????? origin
• ????????????? origin
• strain number
• ???????????????? ???
• antigenic subtype designations ??? hemagglutinin
  ??? neuraminidase glycoproteins

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???????? A/swine/Iowa/15/30 (H1N1)

• type A influenza virus ?????????????? Iowa
  ?????.?. 1930, ???????????????? laboratory
  reference number 15 ????? hemagglutinin subtype
  1 ??? neuraminidase subtype 1 surface
  glycoproteins
• ?????????????? host-of-origin ???????????????????
  ??

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Etiology
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• Hemagglutinin ???? rod
• neuraminidase ???? spikes
• Influenza virus ?????????????????? 10 ????
• ???? 2 ?????????? HA ??? NA ??????????????????????
  ??? (glycoproteins) ???? 2 ???????????????????????
  ???? serotypes ??? influenza A virus
• M1 ??? M2 ???? matrix proteins ???? types A, B
  ??? C ????????? nucleoproteins

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????????????????? antigenic ???????? HA ??? NA

• Antigenic drift ?????????????????? point mutation
  ?? viral RNA segment ??? coding ?????? HA ??? NA
  ????????????? antigenic change ??? minor ???
  surface glycoprotein
• Antigenic shift ????????????????????????????????
  ?? type A influenza virus ???????? ????? subtype
  A ???????????????????? ????????????????????????
  subtype HA ??? NA

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Pandemic influenza

• ????????????? ???? pandemic 3 ????? Spanish Flu
  (????? 40 ?????????? 1918-1919), Asian influenza
  (?? 1957), Hong Kong influenza (?? 1968)
• ???????????????????????????? gene ??????????
  H-component

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Spanish influenza
pandemic ???? 1918-19 ??????? H1N1
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?? 20 ????????? ?? 1918 clinical swine
influenza ??????????
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Influenza Pandemics 20th Century
Credit US National Museum of Health and Medicine
1918 Spanish Flu
1957 Asian Flu
1968 Hong Kong Flu
20 - 40 million deaths
1 - 4 million deaths
1-4 million deaths
A(H1N1)
A(H2N2)
A(H3N2)
Source WHO
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??????????????????????????????? 1997

• influenza subtype A(H5N1) ??????????????????
  ????????????? 1997 (?????? 18 ?? ??? 6 ??) ???
  2003 (?????? 2 ?? ??? 1 ??)
• ????? H7N7 avian influenza strain ????
  ?????????????????????????????? species ?????????

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Asia Week 1998
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• ??????????? H5N1 ??? Man-to-man transmission
• ?????????????????????????????????? ????????????
  pandemic ???
• ????????????????? Genetic ????????????? 7
  ????????????? reassortment ??????? influenza
  virus ???????????? ?????????????????????????
  H5N1-virus ???????????? pandemic
  ????????????????????

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20 ??.?. 40 (1997) influenza vaccine 97-98
??????????

• A/Wuhan/359/95 (H3N2) -like strain
• A/Bayern/7/95 (H1N1) -like strain
• B/Beijing/184/93 -like strain
• ?? 1997 ?????????????????????? H5N1

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• ?? 1996 ??????????????????? conjunctivitis
  ?????????????? avian virus ??????? H7 ??? N7
  ???????????????????? H7N7 ????????????????????????
  ????????? 1995

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???????????????????????????????????

• ????????????.?. 46
• H7N7
• ??????????????? 83 ??? ?????? (79 ???) ????
  conjunctivitis
• 13 ???????????? mild influenza-like illness
• ????????????????????????????? 2 ????????????????
  minor respiratory disease ???????????????????????
  human-to-human transmission

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Human influenza
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????????????????? (??)

• ?????????? 1-3 ???
• ????????????? ???????????? ???????? ??
  ???????????????????????
• ????????????????????? 5 ??? ??????? ??????
• ?????????????????????? ???????????????????????????

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• Influenza ???????????????????????
  ??????????????????????????????????????? 14 ???
  point prevalence ??? incidence ???????????????????
  ???????????????????????? pandemic, epidemic ????
  inter-epidemic

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• ??????????????????????? ??? ???? just
  ??????????????????????
• Virus shedding ???? expose 1-3 ??? ??????????????
  1 ??????? 2-3 ??????? ????????????????????????
  ???????? ?????? 2-3 ???????? ???????????? 14-20
  ??????? exposure

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• ????????????????????????????????? (???????? -
  ??????) ?????????????????????????? ????
  ??????????????????????????????????????????
  ?????????????????????
• Reyes syndrome ???????????????????????????????????
  ????????????????? aspirin ??????????????? CNS ???
  liver ???????????? influenza B ??????? influenza
  A (??????? aspirin ??????????????????? 12 ??)

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Epidemiology ???????????????????????????????????

• Type A influenza worldwide
• sporadic bi-directional transmission ???
  influenza A viruses ???????????????????

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• Type A influenza virus ?????????????????????????
  ???????????????????????? ??? ???? guinea fowl,
  ??? captive game birds, ??? wild free-flying
  birds (???? ???? ???? ???????, shore birds,
  ????????), ????? caged exotic birds ????????
• Waterfowl ???? natural reservoirs ??????
  influenza A virus

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Edematous, cyanotic comb and wattles of a
chicken.
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Bloody cloaca ????????????????
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Haemorrhage ??????????? ??????????? ceca ????
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Transmission

• Inhalation ??????????????????????????????????
  conjunctival
• ????????????????? fomite-associated virus
• ???? ???????? ???/???? ????????????? fomites
  ??????????????? fecal material

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Animal infections

• Incubation period 1-4 days ???????????????????
  ??, apathy, conjunctivitis, rhinitis, nasal
  discharge, anorexia, ?????????????????
  ????????????????? ??? stiffness
• ???????????????? ????? ??????????? paroxysmal
  coughing

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• ??????? ?????? 7-8 ?????????????? (??? recover
  ?? 2-3 ???????)

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• ?????? ??????????????? frothy white ???? bloody
  nasal discharge, muscle tremors, ????????
• ?? ??????????? ???????????????????????????????
  ???/???? ????? ???????????????????????????????????
  ???????????? ?????? ??????????????

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Diagnosis

• ?????
• ?????????????? ????????
• ??????????????
• ????????? hemagglutinin inhibiting ????
  complement fixing antibody titers ????? fourfold
  ??????????????????? 14-21 ??????? acute phase
  serum

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• ELISA
• ???????? virus ?????????? pharyngeal ????
  tracheal swabs ???? throat washing ??????? lung
  tissue ??????????? 3 ????????? onset

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Prevention

• Bio-security programs ?????????????????????????
  ???????????? ?????????????? ?????????? contact
  ??????????????????????????????????
  ???????????????????????????????????
  ??????????????????????????? 30 ???
  ???????????????
• ????????

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Strain ?????????? inactivated vaccine

• ??????????? 3 ?????
• influenza A 2 ???? (H3N2, H1N1) ??? influenza B
  1 ????
• ??????????????? antigenic variant ????????????

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??????????

• ????????????????? ?????????????????????????
  strain ?????????? ????????????????????????????????
  ???????????? ?????????????????????
  ??????????????????????????????? ??? strain
  ?????????????????????
• ?????????????????????????????? ???????????????????
  ?????????????? (?????? ?????????? ??? ???????)

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Family trees for type A viral strains from 11
consecutive flu seasons with each branch
representing a new mutant strain. (Robin Bush)
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influenza vaccine 2003-2004 (46-47) ??????????

• A/New Caledonia/20/99(H1N1)-like virus
• A/Moscow/10/99(H3N2)-like virus
• B/Hong Kong/330/2001-like virus
• ???????????????????? A/Panama/2007/99.
  ????????????????????? B/Shandong/7/97, B/Hong
  Kong/330/2001, B/Hong Kong/1434/2002.

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?????????????????????????????

• ????????? WHO
• ??? Detect ???????????????? (throat secretion,
  paired sera) ????? ref. Lab. ??? Atlanta, USA
  London, UK Melbourne, Australia
• ??????????????????
• ???????????????????????????? ?????????????????????
  ?????????????????????????????

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Avian influenza
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Safe from Farm to Table
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AVIAN FLU OUTBREAKTHAILAND,DEC.2003-MAR.2004

• 12 cases in 9 provinces.
• Male Female 21
• Median age 10 (2 - 58) Y olds.
• 8 died (66.7)
• Age lt 15 Y 85.7 Age gt 15 y. 40.0

Area of poultry outbreak
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Avian flu cases by date of onset, Thailand, Dec.
2003 - Mar. 2004
?? 12 cases
Culled period
No. of cases
31 Jan - 1 Feb
30 - 31 Dec
15 - 16 Jan
26 - 27 Dec
11 - 12 Jan
3 - 4 Mar
27 - 28 Jan
24 - 25 Feb
19 - 20 Jan
23 - 24 Jan
20 - 21 Feb
28 - 29 Feb
12 - 13 Feb
7 - 8 Jan
16 - 17 Feb
3 - 4 Jan
8 - 9 Feb
4 - 5 Feb
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Poultry exposure history
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Univariate analysis results
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??????????????????????????????
????????? Thailand's chicken exports will slide
21.9 per cent in 2004 because as a result of the
outbreak of highly pathogenic avian influenza
that swept Asia earlier in the year, according to
a Dow Jones Newswire report. The value of the
lost chicken exports was USD 965 million.
Thailand is the fourth largest chicken exporter
in the world behind the United States,Brazil, and
China. Many countries banned imports of Thai
chickens after the avian flu outbreak in
Thailand was confirmed 23 Jan 2004. However,
cooked chicken products are being imported by
some major buyers such as Japan and countries
belonging to the European Union, which consume
39 and 54 per cent, respectively, of Thai cooked
chicken exports. (Promed 4/23/04)
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• ??????????????????????????????
• ??????????????????????????????????????????????
• ??????????? ??????? ?????????????????????
• ???????????????????????????????????????
  ?????????????????????
• ??????????? ??????????????? ????????????
• ????????????????????????????????????????????
• ??????????????????????????????????????????????
• ??????????????????????????????????????????????

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??????????????? ???????????????????????
????????????????? ?????????????????
????????????????????????????????????????????
??????
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?????????? ?????? Emerging Infections ??? SRRT
S Surveillance (early detection) R Risk Factor
assessment R Response before risk (prompt
proper response) T Thailand Healthy by
Epidemiology
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Migratory Birds Flyway
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?????????????????????? ?, ????????? ?? 2547
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Case definition ??????

• ???????????? (suspect) ???????????????????????????
  ???????
• ??? (????????????????????????????????? 38 ????)
  ???????
• ???????????????????? ????????????? ?? ??????????
  ??????????????????????????????????????????
  ???????
• ??????????????????????/????????????????? 7
  ??????? ???? ???????????????????????????????????
  14 ??????? ???? ??????????????????????????????????
  ?????????????????????????????????????

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• ???????????????? (probable) ??????????????????????
  ?????????????????????
• ??????????????????????? ??????????????????????????
  ????? A ??????????????????????????????????????????
  ??????????? ????
• ??????????????????????? ????
• ?????????

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• ????????????? (confirm) ?????????????????????
  ?????????????????????????????????????????? A(H5)
  ???????????????????????????? ???????? PCR
  ????????????????
• ????????????????? (exclude) ??????????????????????
  ????????????? ???? ???????????????????????????????
  ??????????????????????

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??? ??. ?????? ???????

• Avian influenza viruses from Thailand are
  genetically very similar to the viruses isolated
  from humans in Vietnam (2004) as well as two
  human virus isolated from two patients in Hong
  Kong (2003)
• Low pathogenic avian influenza virus was also
  found (H4)

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???????????????

• ????????????????????????????????????????
• ???????????????????????????
• ?????????????????????????
• ??????????????????????????????
• ?????????????????????????????????????????????
• ????????????????????? (??????????)

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?????????????????????????????????????????????????
????????????
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?????????????????????????????

• Surveillance Pro-Active, Active, Passive
• Stamp-out, Pre-emptive culling, Test and cull
• Disinfection of infected premises
• Quarantine, Movement control

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The First HPAI case
23/01/2004
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Initial Surveillance

• 161 cases (village, farm)
• 40 provinces
• 71 districts

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H5N1 was isolated from
Broiler 19
Duck 11
Layer 12
Goose 3
Native Chicken 107
Turkey 3
Quail 9
Peacock 2
Total 161 cases
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Second Surveillance

• Areas surrounding stamped out zone
• (gt5-10 Km radius)
• Suspected areas
• (eg. low production, cases or deaths with
  other disease)

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Second Surveillance

• 18 positive from 8,500 samples (20 Feb 04)

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Second Surveillance

• 17 cases locate in the
• previously positive provinces (40 prov.)
• One new case in one new province
• (20 Feb 2004)

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The First HPAI case
Initial Surveillance
Second Surveillance
Second Surveillance
Second Surveillance
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Active Clinical Surveillance

• Symptoms
• Sudden death 70, neuro 20 , GI 20, resp 20...
• Case definition (6)
• death gt10 /d, acc. death gt 40 / 3 d
• Stamp-out suspected farms based on clinical
  (within 24 hr)